The major objective of this research proposal is to study radiation-induced thyroid cancer by a coordinated program of clinical and basic endocrinological investigations. The clinical studies are designed to determine the current risk and continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approaches to treatment. This will be accomplished by a longitudinal study of patients who have been evaluated at Michael Reese Hospital because of history of childhood head or neck irradiation. Of 5,200 patients who were so treated, 1,700 already have been examined and another 1,400 have been contacted by mail. Among these examined, a 31% prevalence of nodules was found, and among those who had surgery, a 32% rate of carcinoma was determined. Follow-up examinations of those patients will provide the information necessary to develop clinical guidelines for the care of persons with a history of head or neck irradiation. Laboratory studies will focus on the role of plasma thyroglobulin in the diagnosis of thyroid tumors. Detailed studies of the molecular properties of plasma thyroglobulin will be undertaken in order to improve its diagnostic usefullness and to understand how it enters the circulation. In addition, an in vitro system will be used to determine at what point thyroglobulin is released from the thyroid into the circulation. The Wollman transplantable thyroid tumor line 1-1C2 will be used as a model system to study plasma thyroglobulin and thyroid cancer. Studies will be undertaken in this system to characterize the abnormal thyroglobulin in the circulation, the mechanism leading to its release into the circulation, and its sensitivity in reflecting changes in the tumor.